Oxytocin Receptors in the Anteromedial Bed Nucleus of the Stria Terminalis Promote Stress-Induced Social Avoidance in Female California Mice.
Oxytocin Receptors in the Anteromedial Bed Nucleus of the Stria Terminalis Promote Stress-Induced Social Avoidance in Female California Mice.
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DOI：
10.1016/j.biopsych.2017.08.024
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发表时间：
2018-02-01
影响因子：
10.6
通讯作者：
Trainor BC
中科院分区：
文献类型：
--
作者：
Duque-Wilckens N;Steinman MQ;Busnelli M;Chini B;Yokoyama S;Pham M;Laredo SA;Hao R;Perkeybile AM;Minie VA;Tan PB;Bales KL;Trainor BC
神经肽催产素（OT）是社会和情感行为的关键调节因子。OT的影响是依赖于上下文的，有人提出，OT增加了积极和消极的社会线索的显着性。在这里，我们测试是否终纹床核（BNST）介导的OT的焦虑作用。首先，我们研究了全身给予OT受体（OTR）拮抗剂L-368，899对暴露于社交失败的雄性和雌性加州小鼠的社交行为的影响。我们研究了L-368，899对G蛋白活化的影响，并使用EGR 1免疫组织化学鉴定了OTR作用的潜在位点。最后，我们检查了在BNST中输注L-368，899对行为的影响。单剂量全身性L-368，899增加了应激雌性动物的社交方式，减少了未经历失败的雄性动物的社交方式。L-368，899阻止OT激活G蛋白，并且在不存在OT的情况下不激活G蛋白。鼻内OT，这减少了社会的做法，在女性，但不是男性，增加EGR 1免疫反应性的核延髓（NAc）的核心和前内侧BNST的女性，但不是男性。在前内侧BNST（而不是NAc核心）中输注L-368，899的应激雌性动物增加了社交途径并降低了社交警惕反应。我们的研究结果表明，前内侧BNST的OTR激活诱导了一种警惕性反应，在这种反应中，个体避免，但参加不熟悉的社会环境。我们的研究结果表明，OTR拮抗剂可能有未被重视的治疗压力引起的精神疾病的潜力。
The neuropeptide oxytocin (OT) is a key regulator of social and emotional behaviors. The effects of OT are context-dependent, and it has been proposed that OT increases the salience of both positive and negative social cues. Here we tested whether the bed nucleus of the stria terminalis (BNST) mediates anxiogenic effects of OT. First, we studied the effects of systemic administration of an OT receptor (OTR) antagonist L-368,899 on social behavior in male and female California mice exposed to social defeat. We examined the effect of L-368,899 on G protein activation and used EGR1 immunohistochemistry to identify potential sites of OTR action. Finally, we examined the effects of L-368,899 infused in the BNST on behavior. A single dose of systemic L-368,899 increased social approach in stressed females and decreased social approach in males naïve to defeat. L-368,899 prevented OT activation of G proteins, and did not activate G-proteins in the absence of OT. Intranasal OT, which reduces social approach in females but not males, increased EGR1 immunoreactivity in the nucleus accumbens (NAc) core and anteromedial BNST in females but not males. Stressed females that received an infusion of L-368,899 in to anteromedial BNST but not the NAc core increased social approach and decreased social vigilance responses. Our results suggest that OTR activation in anteromedial BNST induces a vigilance response in which individuals avoid, yet attend to unfamiliar social contexts. Our results suggest that OTR antagonists may have unappreciated therapeutic potential for stress-induced psychiatric disorders.
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DOI：
10.1038/npp.2009.109
发表时间：
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期刊：
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影响因子：
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DOI：
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发表时间：
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影响因子：
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作者：
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